In this application, we propose the purchase of a laser scanning confocal microscope and multiphoton imager, the Leica TCS SP5 Multiphoton Imager. The purpose of this imager is to 1) replace an aging conventional laser scanning confocal microscope, and 2) expand and upgrade the imaging capabilities of the Confocal Core Imaging Facility at the University of Mississippi Medical Center (UMMC). The University of Mississippi Medical Center is the only academic health center in Mississippi and there are currently no multiphoton microscopes in the State of Mississippi. UMMC has assembled a productive group of NIH- funded researchers whose research would be greatly advanced with access to state-of-the-art imaging facilities. The current Confocal Core Facility was established ten years ago by UMMC with the purchase of the Leica TCS SP2. Day-to-day operations, including routine maintenance and repairs, have been supported by institutional resources and by the Program Project Grant in the Department of Physiology and Biophysics (PO1 HL051971-18). The Confocal Core Imaging Facility has been an essential research tool to numerous NIH funded investigators at our institution. The facility is also available to other investigators at UMMC and local institutions, thus increasing opportunities for competitive research funding for other investigators. The Confocal Core has been vital to the advancement of scientific research at our institution; confocal imaging has been used to elucidate structure-function relationships, protein- protein interactions, ion flux, intracellular trafficking of various proteins and to quantfy changes in oxidative stress and gene expression. However, confocal imaging technology has advanced significantly in the last nine years with increases in sensitivity, speed and laser penetration. Sensitivity limitations in our older instrument prevent us from taking advantage of high-sensitivity, high-resolution imaging capabilities. Furthermore, our aging instrument prevents members of our research community from taking advantage of new imaging technologies, specifically multiphoton imaging technology which reduces tissue damage and photobleaching and offers imaging deeper into tissues. The new imaging system we are requesting is specifically designed for high-speed, high-structural resolution confocal imaging and intravital multiphoton microscopy. The instrument will be used for a collection of research projects throughout the campus, each directed to significant disease or health-related physiological processes. The proposed instrument will be used in studies addressing hypertension, diabetes, renal angiogenesis, neurodegenerative diseases, renal injury and tubular function, lupus erythematosus, cardiac angiogenesis, tissue repair and cancer. PUBLIC HEALTH RELEVANCE: The Confocal Core Imaging Facility at the University of Mississippi Medical Center is housed in the Department of Physiology and Biophysics in the School of Medicine and managed by the applicant Dr. Heather Drummond and contains an aging Leica TCS SP2 laser scanning confocal microscope purchased in 2001. Members of several departments including Physiology and Biophysics, Biochemistry, Pharmacology, Microbiology, Anatomy, Nephrology, Pediatrics and members of the Dental School use the facility. The new Leica SP5 Multiphoton Imager requested in this application will be integrated into the current Confocal Core Imaging Facility at the University of Mississippi Medical Center and will be used to expand usage and upgrade imaging capabilities (speed, sensitivity, infrared) to those of live cell and whole animal imaging.